A biomechanical perspective of the carpal tunnel (CT) is reviewed that lends itself to an understanding of carpal tunnel syndrome (CTS) from a broader pathophysiological perspective than focusing narrowly or solely on nerve disturbance in the extremity. A wider integration of physiological systems in the etiology and maintenance of CTS is proposed that links muscular dysfunction in the neck and possibly elsewhere to dysfunction at the CT. A significant subset of individuals who develop CTS have a primary contribution from muscular dysfunctions rather distal to the CT itself. Neurophysiological dysregulation of normal inhibitory feedback at the level of the motoneuron pool specifically involving gamma motoneuron impulses may be a primary contributing mechanism. Empirical demonstration of amelioration of CTS symptoms by means of surface electromyography (sEMG) retraining of dysfunctional neck muscle patterns is reviewed as support for the hypothesized link. The specific retraining techniques are described. Future conceptual and research directions are noted.